Leprosy
Mailing List – September 20, 2016
Ref.: (LML)
A Dual Crisis: The Chemotherapy of MB Leprosy and
Leprosy Control
From: Robert Gelber, San Francisco, California
Dear
Pieter,
As a background
here and to add information to these comments, I, with the gracious permission
of Paul Saunderson, wish to share as an attachment (15 MB) an editorial co-authored by
myself and Jacques Grosset, published in Leprosy Review 2012, entitled: “The
Chemotherapy of Leprosy: An Interpretive History”.
There is a
compelling literature that the therapy of MB leprosy and particularly in those
with a high bacterial burden, whether it be with other rifampin-containing
regimens or two-year WHO MDT, results in an unacceptably high relapse
rate.
That remains
underappreciated and without address for several reasons:
-
MB
relapse following MDT and other rifampin-containing regimens appears first six
years after the completion of therapy and most commonly ten or more years
thereafter when patients are no longer accessing leprosy care, and, also, MB
relapse is rarely associated with neuropathy or deformity.
-
Furthermore, MB relapse
may not be reported because there is shame that non-compliance might have been
its cause or a loss of confidence that the promised cure was not
realized.
-
Also, if a patient
presents to another service provider, a history of prior treatment may not be
elicited.
-
Contributing to the lack
of recognition of MB relapsed leprosy in the medical literature is that few
studies, especially with the regular and prolonged follow-up required to assess
the problem, have been conducted and published.
-
Importantly, in the
current climate where leprosy care is increasingly performed by the general
health services, we found those services recognized considerably fewer relapses
than those conducted by seasoned leprologists.
There is some
reason for hope that an alternative MB MDT regimen might prove reliably
curative. This prospect should be urgently studied. In fact, the short-term
chemotherapy of tuberculosis required two bactericidal agents, where MB MDT
contains but one, rifampin. As moxifloxicin has proved both in mice and
clinical trials to be equipotent to rifampin, a rifampin / moxifloxicin regimen,
containing one or more other agents similarly proved more active than dapsone
and clofaximine, might make a finite therapy of MB leprosy possible – a most
important goal. For this, WHO MDT has failed. For that reason, I currently
recommend for MB patients continued life-long dapsone
treatment.
Unfortunately,
for almost the past two decades, I know of no new studies for leprosy of the
activity of antimicrobials in mice, particularly those active against M.
tuberculosis and almost none in leprosy patients. Clearly, chemotherapy
studies have lost their import. This is not surprising as the efficacy of MDT
in all leprosy patients has largely been unchallenged. Future studies should be
a priority, but these are hindered as there are few mouse footpads worldwide to
monitor them, and especially with the necessary experience and capacity. If
this is not urgently corrected, soon there may well be none at all and with the
trained technologists having experience with the painstaking methodology of that
system which has been largely unpublished. Though several in vitro methods
dedicated to replace the mouse footpad have some promise, none have been
established anywhere near the sensitivity of the mouse footpad (one to a few
bacilli).
On an entirely
separate note, as we pointed out in the attachment for India, and as Karin Smith
et al. demonstrated, occurred worldwide (PLOS Neglected Tropical
Diseases, April 23, 2015), the dramatic fall in the incidence of new cases
of leprosy by a factor of two or three in the five or six year period of 2000 –
2006, was not plausible. The reason for this unreasonable fall in leprosy
incidence must surely be loss of operational infrastructure. Both the
attachment and this referenced article point to the road to redress this
frightening trend which will surely lead not only to delayed or absent treatment
for millions, but the threat those untreated patients pose to infect others
and to further heighten the leprosy burden. Furthermore, the loss of
infrastructure has importantly caused a greater incidence of deformity in the
minority fortunate enough to have been recognized and placed on
treatment.
Robert Gelber
University of
California
LML - S Deepak, B Naafs, S
Noto and P Schreuder
LML
blog link: http://leprosymailinglist.blogspot.it/
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